Inorganic ions are an essential requirement for life and are found in large amounts in drinking water, blood and cells of an organism as well as in the environment. For example, the presence of many ions, e.g. sodium, potassium, magnesium, and calcium, inside and outside of the cells is essential for a living organism. Consequently, a measurement of the ion concentration in the blood and in blood cells of animals and human beings is of high importance for a large variety of body functions.
Normally lithium is not at all or solely as a trace element present in the blood plasma, but it is also used as a drug to treat bipolar mood disorder. It is estimated that worldwide over one million people take lithium on a daily basis. A disadvantage in the use of lithium is the very low therapeutic index, i.e., the ratio between the toxic concentration and the therapeutic concentration. Most patients respond well to a blood plasma concentration of 0.4-1.2 mmol/L lithium while a lithium concentration of above 1.6 mmol/L is considered toxic. A prolonged high blood lithium level can result in permanent damage to the nervous system and even death. Monitoring of the lithium concentration during treatment is therefore essential, with regular checks every couple of months to keep the lithium level at desired level.
The direct measurement of lithium in whole blood and the determination of inorganic cations in blood plasma have been described and demonstrated by E. Vrouwe et al. in Electrophoresis 2004, 25, 1660-1667 and in Electrophoresis 2005, 26, 3032-3042. Using microchip capillary electrophoresis (CE) with defined sample loading and applying the principles of column coupling, the concentration of alkali metals in the blood was determined in a drop of whole blood. Blood collected from a finger stick was transferred onto a chip without extraction or removal of components from the blood. The lithium concentration can be determined in the blood plasma from a patient on lithium therapy without sample pre-treatment. Using a chip with conductivity detection, a detection limit of 0.1 mmol/L has been obtained for lithium in a 140 mmol/L sodium matrix.
In these disclosures, the components of the blood sample are separated electrophoretically inside a micro-channel. A double T injection geometry is used to select the ion components of interest and to guide them to detection electrodes.
A method and an apparatus for measuring the ion concentration in liquid samples is disclosed in the co-pending PCT application PCT/EP2006/011148 the teachings of which are included by reference herewith. This PCT application describes an apparatus for the measurement of a concentration of a charged species in a sample, the sample comprising a plurality of types of charged species and at least one insoluble component, the apparatus comprising at least one channel with at least one opening with a filter function, at least two electrophoresis electrodes arranged along the at least one channel, and at least one sensor for measuring at least one type of charged species in the at least one channel.
The dimensions of the opening and the channels used in such an apparatus are usually very small in order to reduce the amount of liquid necessary and the size of the apparatus. Typical channel dimension are in the order of less than 1 cm in width and less than 100 μm in depth. Consequently the apparatus can be quite small as well in order to minimize the amount of material used for the apparatus. The material is often expensive as for example glass.
The apparatus should also be easily usable by a patient or other user. In particular, the patients suffering from bipolar mood disorder or similar illnesses, often suffer from quivering or shaking hands and encounter problems in handling small pieces.
Furthermore blood sample and consequently the channels can be easily contaminated by blood or other liquids and can not be reused without intensive cleaning and sterilisation.
In contrast, the known prior measurement devices are complex microfluidic and electronic components that are expensive and therefore not suited for one-time use only.
It is an object of the present invention to provide a device and a method for easy handling of liquid sample measurement devices for measuring small samples.
It is a further object of the invention to provide measurement devices that can be used as disposables while advanced measurement techniques can be employed.